Studies of immunoregulation in health and disease are being pursued both in vivo and in vitro. For in vivo work immunoregulation is being examined in normal humans and in patients with suspected immunoregulatory diseases such as sarcoidosis and leprosy using two techniques. The first involves the measurement of spontaneous suppressor cell activity with fresh samples of blood. We are concentrating on freshly isolated T gamma cells and their ability to induce spontaneous suppression and comparing this ability to the response of the same cells to Concanavalin A. The ratio of induced suppression to spontaneous suppression gives, we feel, the better index of suppressor cell activity in vivo than just using one parameter. In vivo we are concentrating on the use of cyclophosphamide as a probe to dissect immunoregulatory mechanisms for control of delayed hypersensitivity and the Arthus reaction. We have shown in guinea pigs that all forms of delayed type hypersensitivity can be enhanced by cycolphosphamide but are concentrating on the enhancement of tuberculin type hypersensitivity. Cyclophosphamide is able to enhance classical tuberculin sensitivity when the drug is administered in large doses either three days before or one day after immunization. On the other hand, cyclophosphamide is able to completely block antigenic competition between opposing antigens only when given after the administration of the antigen. Yet another immunoregulatory mechanism can be upset by cyclophosphamide in that four hour Arthus reactions in guinea pigs can be markedly enhanced with very small doses of cyclophosphamide given as late as four days after immunization. We are also examining the effects of cyclophosphamide on the production of desensitization or anergy in guinea pigs. Additional studies involving immunoregulation include our examination of the effect on immunoregulatory cells of BCG vaccination in patients with lung cancer and continuing effort to look at the same problem in patients with acute and chronic malaria.